Extreme heat and preterm birth in rural Zimbabwe

Preterm birth is the leading cause of under-5 mortality. There is emerging evidence that heat stress in pregnancy is associated with preterm birth; however, the underlying mechanisms are uncertain. Our hypothesis is that extreme heat propagates induction and amplification of inflammation, and reduced integrity of fetal membranes, leading to premature rupture and preterm birth. An interdisciplinary team of UK and Zimbabwean scientists will: - Determine the relationship between extreme heat and prematurity in rural Zimbabwe. - Explore associations between extreme heat and inflammatory mechanisms underlying preterm birth. - Evaluate the effects of extreme heat, inflammation and mechanical stimulation on structural integrity and function of fetal membranes using a human fetal chip model. First, we will leverage a well-characterised cohort of pregnant women in a rural district of Zimbabwe affected by climate change, to collect longitudinal biological samples, map household locations, and deploy high-resolution sensors to measure temperature and humidity. Second, we will explore associations between extreme heat and preterm birth, and define underlying inflammatory pathways in the maternal systemic circulation and at the materno-fetal interface. Finally, we will use human explant and 3D co-culture models to study the mechanical properties and cellular responses of fetal membranes to extreme heat.